ASSAY FOR IMMUNE CELL RECOVERY

Detailed Action Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1, 29-30, 43, 57-60, and 62-75 are pending. Claims 65-75 are new. Applicant's election with traverse of Group 1, claims 1-3, 5, 7-9, and 13, in the reply filed on 04/09/2025 is re-acknowledged. The traversal was on the ground(s) that the inventions possess unity of invention. This is not found persuasive because the traversal argument fails to point to any deficiency in the Examiner’s argument that the inventions, lacking unity of invention for lack of a special, shared technical feature, upon which the restriction requirement was based. The requirement is still deemed proper and is therefore remains FINAL. Claims 29-30, 43, and 63-64 remain withdrawn and newly added claims are 71-75 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected groups/inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04/09/2025. Claims 2-28, 31-42, 44-56, and 61 are cancelled. Claims 1, 29, 43, 57-59, 62 and 64 are amended. Claims 1 and 57-60, 62, and 65-70 are under examination on the merits. Priority This application is a 371 of PCT/US2020/050112, filed 09/10/2020, which claims benefit of priority to US Provisional Applications 62/898,170, filed 09/10/2019, and 62/904,843, filed 09/24/2019. Maintained-Claim Interpretation Where ‘recovery’ is recited in the claims, recovery is interpreted to mean restoration of immune cell function (such as cytotoxic activity), as supported by exemplary page 11 of the specification (see for example, point 48). The term ‘increased’, in the interest of advancing prosecution, being interpreted to mean any increase relative to a specified control (as is consistent with the entirety of the disclosure, see for example point 13 at exemplary page 3 of the specification). The recitation that the NK cell comprises a CAR NK cell is being interpreted to mean that the NK cell to be frozen, thawed, and assayed in the method of claim 1 comprises a chimeric antigen receptor (CAR) prior to freezing, thawing, and assaying for CD16 expression (see for example, claim 58). The recitation that the NK cell is an expanded NK cell is being interpreted to mean that the NK cell to be frozen, thawed, and assayed in the method of claim 1 has been expanded prior to freezing, thawing, and assaying for CD16 expression (see claim 59). The recitation that the expression level of CD16 on the NK cell within 3 hours after thawing (test cell) is 80% or more of an expression level of CD16 on a control is being interpreted to mean that the measured level of CD16 expression of the test cell is a value which is 80% or more of the measured level of CD16 expression on the control cell (for example, if the control cell had a CD16 expression level of 100, then the test cell level of CD16 expression selected for having an increased CD16 expression correlated with an increased likelihood of recovery would have a CD16 expression level of 80 or higher). Recitations of “lots of cells” is interpreted to refer to lots as disclosed at the second sentence of the background section at page 1 of the specification. This being the only mention/disclosure of “lots”, “lots” are interpreted to refer to a number or plurality of cells that are selected (art teaching selection of cells, a plurality of cells, or a batch(es) of cells would be deemed to anticipate or make obvious this limitation). Withdrawn Objections and Rejections The objections to claims 1, 57-59, and 62 are withdrawn in light of the corrective claim amendments dated 08/03/2026. The rejections of the claims under 35 USC§101 are withdrawn in light of Applicant’s amendments to the claims to add integrating steps of freezing and thawing (in congruence with Applicant’s arguments citing to Rapid Litigation Management Ltd., et al. v. CellzDirect, Inc., et al., No. 2015-1570 (Fed. Cir. Jul. 5, 2016) in the telephonic interviews conducted on 07/3/2026 and 07/24/2026) and in light of a consult with an internal point of contact/expert regarding the Application of 35 §103 on 07/22/2026. The rejections of the claims under 35 USC §103 over Romee et al and Mata et al are withdrawn and replaced with the rejections under 35 USC §103 presented, below, in this Office Action to better account for the altered claim scope and newly added claims resulting from the claim amendments dated 08/03/2026. New-Claim Rejections - 35 USC § 103 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claim(s) 1, 57, 60, 62, 65-66, and 69-70 is/are rejected under 35 U.S.C. 103 as being unpatentable over Romee et al (NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood. 2013 May 2;121(18):3599-608. doi: 10.1182/blood-2012-04-425397. Epub 2013 Mar 13) in view of Mata et al (Effects of cryopreservation on effector cells for antibody dependent cell-mediated cytotoxicity (ADCC) and natural killer (NK) cell activity in (51)Cr-release and CD107a assays. J Immunol Methods. 2014 Apr;406:1-9. doi: 10.1016/j.jim.2014.01.017. Epub 2014 Feb 20) and Min et al (Immune Netw. 2018 Aug 21;18(4):e31. doi: 10.4110/in.2018.18.e31). Regarding claim 1, it is noted that the only explicit, active step is measuring/assaying the amount of CD16 expression with a further implied mental step of comparing the measured amount of CD16 to a control/reference value. The preamble recitation that the selected cell is suitable for use in an immunotherapy is not an active step breathing life and meaning into the claim so as to lend patentable weight. Romee et al teach that CD16 is present on the surface of NK cells and plays an important role in antibody-NK cell mediated cytotoxic activity of the NK cell. Romee et al further teach that the metalloprotease ADAM-17 cleaves CD16 (see for example the abstract at pg. 3599). Note that Romee et al teach measurement of CD16 (see for example Figure 1 and its caption at pg. 3602 and pg. 3604, right hand column). Romee et al further teach measurement of the surface-expressed receptor CD16 using commercially-available antibodies against CD16 and a commercially-available flow cytometer and software (see for example, column 1 at page 3600 under the Antibodies heading and Figure 4 and its caption at page 3604). Romee et al do not explicitly teach a connection between CD16 and freezing and thawing cells or between a freeze-thaw and diminished recovery of cell function. However, Mata et al teach that CD-16 is decreased in frozen and thawed NK cells which have a decreased level of cytotoxic (ADCC) activity (see for example pg. 8). Mata et al further teach that the freeze-thawed NK cells were used either immediately or after overnight incubation, which would read upon and make obvious any use within the time frame of 0-12 hrs (see for example, Figures 2-3 at pages 3-4 and paragraph 1 of column 1 of page 5). While Mata et al may initially appear to show that NK cells used after thawing (not rested) have lower NK cell activity, this is not taken to be a teaching against assaying for CD16 expression within 3 hrs of thawing (in thawed/non-rested cells) because thawed NK cells thawed/non-rested (held to read on being assayed within 3 hrs of thawing) and thawed/rested (held to mean the cells were assayed after 8-12 hours of thawing) were reported to have the same mean CD16 expression (see for example, page 6, paying particular attention to Table 1 and its caption). Romee et al and Mata et al do not teach that the increased level of CD16 expression on NK cells positively correlates with the likelihood of NK cell recovery 24 hours after thawing. However, Min et al assessed the effect of cryopreservation on the expanded NK cells in regards to viability, phenotype, and anti-tumor activity (see for example, page 1/25). Min et al analyzed cryopreserved NK cells not only immediately after thawing but also after incubation for 24 or 48 h with or without IL-2 (500 IU/ml) following thawing. As results, the cell number, viability, and cytotoxic activity of thawed NK cells were not significantly influenced by the incubation time and/or the presence of IL-2 (see pages 8/25-9/25 and Supplemental Fig. 3). It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Romee et al and Mata et al. The artisan would have been motivated to make and use the invention as claimed because Romee et al teach that CD16 is important for NK cell cytotoxic function (as well as how to measure the level of CD16) and Mata et al teach that CD16 is decreased after freeze-thawing cells. The combined disclosures lead the artisan to measure and select (where the generic recitation encompasses any known means in the art, up to and including mental selection) cells with a greater amount (aka an increased amount) of CD16 (so as to lead to a cell (or lot(s) thereof) more likely to function at any point in time including after a potentially membrane-damaging event, such as a freeze-thaw cycle) purely in the interest of optimizing known NK cell function (such as desirable cytotoxic (ADCC) function). The MPEP provides that: "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,” (see MPEP 2112(I)). Therefore, the cited references and teachings are held to make obvious before the effective filing date of the claimed invention the active step of measuring/assaying for the level of a surface-expressed receptor (CD16), comparison of said measurement to some reference/control value, and selection of cells bearing more CD16 as a means of selecting cells most likely to have the greatest degree of (cytotoxic) function (understood to be a cell with a greater likelihood of recovery, see the claim interpretation section of this Office Action). Where the active steps are the same (obtaining the cell, measuring/assaying, and selecting cells) and the starting population is the same (NK cells after a freeze/thaw cycle), the results are presumed to be the same. It is noted that cells selected based upon a higher CD16 expression level are suitable for immunotherapy as claimed, such that prior art teaching or making obvious such selection makes obvious the instant claim (see for example, the claim interpretation section above). Romee et al and Mata et al teach/make obvious that increased CD16-expression positively correlates with the likelihood of recovery up to 12 hrs post-thaw. The artisan would have expected this positive correlation (an effect of practicing the method of claim 1, notably not an active step) to extend to 24 hrs post-thaw, predictably, because Min et al, examining cryopreserved NK cells (post freeze-thaw), looked at NK cells immediately post-thaw, 24 hrs post-thaw, and 48 hrs post-thaw and found that cytotoxic activity was not different at any of the three time points (indicating that cytotoxic activity is relatively stable such that cells with indicators of higher actual or likely recovered cytotoxic activity would predictably exhibit that property across a 48 hr post-thaw period. Therefore, the artisan would have been motivated to practice the active step of obtaining one or more frozen NK cells thawed for 3 hours or less, assaying the thawed cells within 3 hours of thawing to determine an expression level of CD16 compared to a control, and selecting thawed NK cells expressing an increased level of CD16 relative to expression on a cell-surface-damaged control. Where the selected cells are part of an immunotherapy composition, maintenance of their cytotoxic function would have been considered an obvious and desirable component of viability of the cells to be selected. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date. It is noted that the correlation step is not an active step, but is more proper categorized as characterizing and observed relationship between the expression of CD16 and ‘viability’ through methods made obvious by the above cited prior art where discovery of said relationship does not make patentable a method which the prior art teaches as motivates as obvious. Regarding claims 57 and 66, Mata et al teach that the frozen PBMCs (including NK cells) were thawed using a water bath (see for example, paragraph 1 of column 1 of page 5). Regarding claim 60 and 69, Mata et al teach analysis of CD16 expression using flow cytometry (see for example, section 2.5 at columns 1-2 of page 5 and Figure 2 and its caption at page 3; see also, for example, Romee et al at column 1 at page 3600 under the Antibodies heading and Figure 4 and its caption at page 3604). Regarding claim 62, Mata et al appears to further teach that cells frozen and thawed are capable of having as much and even more CD16 expression as measured by flow cytometry (see for example, Table 1 and its caption at page 6). Mata et al does not point to an increase of 80% or more being particularly significance. However, the combined references point to the significance of CD16 expression for NK cell activity and show that sufficient CD16 expression is important for NK cell function and cytotoxicity. The artisan, in light of Mata using a fresh NK cell (not frozen and thawed) as a positive control/baseline, would have understood the desirability of selecting (not a required active step of the claim as drafted in claim 62) an NK cell with a higher (close to the positive control-fresh cell expression level) expression of CD16 would be more likely to have or recover immune function(s) associated with NK cells (such as cytotoxic functionality). It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Romee et al, Mata et al, and Min et al. The artisan would have been motivated to make and use the invention as claimed because Romee et al teach that CD16 is important for NK cell cytotoxic function and Mata et al teach that CD16 is decreased after freeze-thawing cells. The combined disclosures lead the artisan to measure and select for cells with a greater amount (aka an increased amount which would have been understood to be an amount up to the expression observed in positive control (non-frozen-thawed/fresh cells)) of CD16 in order to select for a cell with a greater likelihood of having/recovering cytotoxic (immune) function. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references. Regarding claim 65, the primary difference between the method of instant claim 1 and instant claim 65 is selecting one or more thawed, viable NK cells versus selecting manufacturing lots of thawed, viable NK cells. The active steps and reagents are the same. There is no reason to believe the methods of the prior art would function differently for selection of one or more NK cells versus lots of NK cells. Therefore, claim 65 is deemed obvious for the same reasons claim 1 is deemed obvious over the cited prior art references. Regarding claim 70, where the cells of Mata et al were thawed, they logically must have first been frozen. Therefore, Mata et al is deemed to implicitly teach a step of freezing the one or more K cells prior to thawing them in step a of claim a of either of claims 1 or 65 (noting that claim 70 is drafted to depend from claim 65, but noting that the language of ‘one or more NK cells tracks more closely with and more clearly derives antecedent basis from, claim 1). Therefore, claim 70 is made obvious over the combined cited prior art for the same reasons that claims 1 and 65 are deemed to be made obvious with a reasonable expectation in light of the combined prior art references prior to the effective filing date. Claim(s) 58 and 67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Romee et al, Mata et al, and Min et al, as applied to claims 1, 57, 60, 62, 65-66, and 69-70 above, in further view of Hermanson et al (Front Immunol. 2015 Apr 28;6:195. doi: 10.3389/fimmu.2015.00195). Regarding claim 58 and 67, Romee et al, Mata et al, and Min et al teach as set forth above. The combined references do not explicitly teach that the NK cell is a CAR NK cell. However, Hermanson et al teach that chimeric antigen receptors (CARs) have also been evaluated in peripheral blood NK cells (PB-NK cells). In contrast to NK-92 cells, activated PB-NK cells express a wider range of activating receptors, such as CD16. A greater variety of CAR constructs have been used and directly compared in PB-NK cells (see for example, column 2 of page 3). Hermanson et al further teach that NK cells recognize infected or transformed cells through multiple cell surface receptors including, CD16 [the receptor that mediates antibody-dependent cellular cytotoxicity (ADCC)] (see for example, the abstract at page 1). Note that Hermanson et al teach that a disadvantage of a common NK cell line (NK-92 cells) is that they do not express CD16, implicitly teaching that expression of CD16 would be beneficial for a CAR NK cell (see for example, the last paragraph of column 1 of page 2). It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Romee et al, Mata et al, Min et al, and Hermanson et al. The artisan would have been motivated to make and use the invention as claimed because Romee et al teach that CD16 is important for NK cell cytotoxic function (as well as how to measure the level of CD16) and Mata teach that CD16 is decreased after freeze-thawing cells. The combined disclosures lead the artisan to measure and select cells with a greater amount (aka an increased amount) of CD16 (whether that increase is relative to a membrane-damaged cell as the negative control or non-membrane-damage-exposed cell would appear to be irrelevant where the combination of the cited references teach that an increase in the amount of CD16 expression enhances function (so as to lead to a cell more likely to function at any point in time including after a potentially membrane-damaging event such as a freeze-thaw cycle) purely in the interest of optimizing known NK cell function (such as desirable cytotoxic (ADCC) function). Hermanson et al teach that CAR NK cells are helpful in treating cancers (see for example, the abstract at page 1 and column 2 of page 3) and that NK cells expressing CD16 are advantageous for use/incorporation into a CAR NK cell (see for example, the last paragraph of column 1 of page 2). Therefore, the artisan, motivated to make a CAR NK cell for treating cancer, would have been further motivated to select an NK cell expressing CD16 in developing the CAR NK cell. Additionally, the cells of Romee et al would have been understood, in light of the teachings of Mata et al, to have a greater likelihood of recovery (which is interpreted to encompass a restoration of/capacity for immune function) and Romee et al, Mata et al, and Hermanson et al teach that CD16 is positively correlated with NK cell immune function (ADCC/cytotoxicity; see the cited teachings as discussed in the rejections above). Likewise, selection of frozen CAR NK cell based upon an increased CD16 expression would have been understood as obvious in light of the cited prior art teachings in order to select an NK cell most able to function in the therapeutic/cytotoxic process associated with CAR NK therapy, where the inclusion of the CAR would not have been expected to alter predictability of said correlation between CD16 and actual/recovered cytotoxic activity/capacity (immune function). The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date. Claim(s) 59 and 68 is/are rejected under 35 U.S.C. 103 as being unpatentable over Romee et al, Mata et al, and Min et al , as applied to claims 1, 57, 60, 62, 65-66, and 69-70 above, in further view of Lee et al (Sci Rep 7, 11075 (2017). https://doi.org/10.1038/s41598-017-09259-1). Regarding claims 59 and 68, it is unclear what significance the nature of the NK cell (expanded versus non-expanded would have for the practice of the method of instant claim 1. Regardless, Romee et al, Mata et al, and Min et al teach as set forth above. The combined references do not teach that the NK cell is expanded prior to use in the method of claim 1. However, Lee et al teach that an NK cell activating signal is mediated by various NK cell receptors, including CD16, which is responsible for ADCC (see page 1). In particular, CD16 has a unique ability to induce NK cell activation without additional receptor signals (see page 2). Thus, combinations of NK cell-activating receptors, including CD16 can be a promising strategy to induce NK cell activation and expansion. While the level of CD16 did not significantly differ between expanded and non-expanded NK cells, the expanded NK cells had higher levels of other receptors known to act synergistically with CD16 for NK cell activation and immune function (see pages 1-3). It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Romee et al, Mata et al, Min et al, and Lee et al. The artisan would have been motivated to make and use the invention as claimed because Romee et al teach that CD16 is important for NK cell cytotoxic function (as well as how to measure the level of CD16) and Mata teach that CD16 is decreased after freeze-thawing cells. The combined disclosures lead the artisan to measure and select cells with a greater amount (aka an increased amount) of CD16 (whether that increase is relative to a membrane-damaged cell as the negative control or non-membrane-damage-exposed cell would appear to be irrelevant where the combination of the cited references teach that an increase in the amount of CD16 expression enhances function (so as to lead to a cell more likely to function at any point in time including after a potentially membrane-damaging event such as a freeze-thaw cycle) purely in the interest of optimizing known NK cell function (such as desirable cytotoxic (ADCC) function). Lee et al teach that CD16 aids in expansion of NK cells and that expansion increases expression of other receptors which are synergistic with CD16 for NK cell activity/activation. Therefore, the artisan would have expected an expanded NK cell to function in the method of Romee et al, Mata et al, and Min et al and would have understood that using an expanded T cell in the method may further enhance the likelihood of recovery of immune function of the NK cell having increased CD16 (through combining the teachings of Romee et al and Mata et al regarding CD16 and the teachings of synergy from Lee et al). Additionally, the cells of Romee et al would have been understood, in light of the teachings of Mata et al, to have a greater likelihood of recovery (which is interpreted to encompass a restoration of/capacity for immune function) because Romee et al, Mata et al, and Lee et al teach that CD16 is positively correlated with NK cell immune function (ADCC/cytotoxicity; see the cited teachings as discussed in the rejections above). Likewise, there is no reason to believe that the method of Romee et al and Mata et al would not function to predictably identify frozen-thawed, expanded (before or after the freeze-thaw) NK cells which are more likely to have recovered functionality based upon a relatively increased expression of CD16. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references. Applicant’s Arguments and Responses A. Applicant requests withdrawal of the rejections of the claims under 35 USC §103, alleging that the combination of cited prior art does not make obvious a correlation between the likelihood of viable NK cell recovery within 24 hours after thawing. Response: It is noted that a pure correlation would not lend patentable weight as a judicial exception even where said exception is integrated. Furthermore, while discovery of such a correlation is of academic interest, it would not distinguish the claimed method over any prior art method which taches measurement of CD16 on NK or CAR-NK cells as a measure of viability/suitability for immunotherapy within 24 hours post-thaw. For the fullest evaluation of the argument and in the interest of advancing compact prosecution, the Examiner understands and will evaluate the argued limitation to consistent with an understanding that the measurement of CD16 is an active step which guides an active step of selection of cells most likely to be viable within 24hrs post-thaw. All rejections over Romee et al and Mata et al have been withdrawn and replaced with the rejections set forth above, which are deemed to better account for Applicant’s amended claim scope. As noted in the rejections, the correlation to which Applicant points to assert nonobviousness is not an active step and does not require the use of a different reagent or result in a different selected NK cell(s)/lot(s) of NK cell(s). The correlation is more properly categorized as a discovery, but is insufficient to make nonobvious the method taught and motivated by the prior art using the same starting cell population, reagent(s), and active steps. Therefore, the rejections for nonobviousness as set forth in this Office Action are maintained. Conclusion The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. CN105838677 A (citation 2 under Foreign Patent Documents on the 02/17/2026 IDS) is still deemed relevant, but not as closely related to the invention as the cited prior art. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. The examiner can normally be reached on M-F 9:00 am - 6:00 pm EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Ashley Gao/ Examiner, Art Unit 1678 /GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678